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| Title | The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. |
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| Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 3314, Year 2022 |
| Publish date | Jun 8, 2022 |
Authors | L F L Wilson / T Dendooven / S W Hardwick / A Echevarría-Poza / T Tryfona / K B R M Krogh / D Y Chirgadze / B F Luisi / D T Logan / K Mani / P Dupree / ![]() |
| PubMed Abstract | Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of ...Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3's GT47 domain to transfer β-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism. |
External links | Nat Commun / PubMed:35676258 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.43 - 2.93 Å |
| Structure data | EMDB-11923, PDB-7au2: EMDB-11926, PDB-7aua: |
| Chemicals | ![]() ChemComp-MN: ![]() ChemComp-UDP: |
| Source |
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Keywords | TRANSFERASE / glycosyltransferase / heparan / n-acetylglucosaminyltransferase |
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homo sapiens (human)
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